EUS-guided tissue acquisition in the study of the adrenal glands: Results of a nationwide multicenter study.

BACKGROUND: There are limited data about the role of endoscopic ultrasound-guided tissue acquisition (EUS-TA), by fine needle aspiration (EUS-FNA) or biopsy (EUS-FNB), in the evaluation of the adrenal glands (AG). The primary aim was to assess the diagnostic yield and safety. The secondary aims were the malignancy predictors, and to create a predictive model of malignancy. METHODS: This was a retrospective nationwide study involving all Spanish hospitals experienced in EUS-TA of AGs. Inclusion period was from April-2003 to April-2016. Inclusion criteria: all consecutive cases that underwent EUS-TA of AGs. EUS and cytopathology findings were evaluated. Statistical analyses: diagnostic accuracy of echoendoscopist's suspicion using cytology by EUS-TA, as gold standard; multivariate logistic regression model to predict tumor malignancy. RESULTS: A total of 204 EUS-TA of AGs were evaluated. Primary tumor locations were lung70%, others19%, and unknown11%. AG samples were adequate for cytological diagnosis in 91%, and confirmed malignancy in 60%. Diagnostic accuracy of the endosonographer's suspicion was 68%. The most common technique was: a 22-G (65%) and cytological needle (75%) with suction-syringe (66%). No serious adverse events were described. The variables most associated with malignancy were size>30mm (OR2.27; 95%CI, 1.16-4.05), heterogeneous echo-pattern (OR2.11; 95%CI, 1.1-3.9), variegated AG shape (OR2.46; 95%CI, 1-6.24), and endosonographer suspicion (OR17.46; 95%CI, 6.2-58.5). The best variables for a predictive multivariate logistic model of malignancy were age, sex, echo-pattern, and AG-shape. CONCLUSIONS: EUS-TA of the AGs is a safe, minimally invasive procedure, allowing an excellent diagnostic yield. These results suggest the possibility of developing a pre-EUS procedure predictive malignancy model.

A Spanish multicenter study to estimate the prevalence and incidence of chronic pancreatitis and its complications.

BACKGROUND AND OBJECTIVE: No nation-wide epidemiological study on the incidence and prevalence of chronic pancreatitis (CP) had been thus far carried out in Spain. Our goal is to estimate the prevalence and incidence of CP, as well as to determine the diagnostic and therapeutic criteria used in Spanish pancreas units. METHODS: An observational, descriptive study of hospital pancreas units in Spain. CP-related epidemiology, etiology, manifestations, diagnostic tests, functional complications, and treatments were all assessed using a structured questionnaire. Overall results were estimated by weighting cases in each site. RESULTS: Information was collected from six pancreas units with a sample frame of 1,900,751 inhabitants. Overall prevalence was 49.3 cases per 105 population (95 % CI, 46 to 52) and incidence was 5.5 cases per 105 inhabitant-years (95 % CI, 5.4 to 5.6). Most common etiologies included tobacco and alcoholism, which were associated with three in every four cases. The most prevalent symptoms were recurring pain (48.8 %) and chronic abdominal pain (30.6 %). The most widely used diagnostic method was echoendoscopy (79.8 %), CT (computerized tomography) (58.7 %), and MRI (magnetic resonance imaging)/MRCP (magnetic resonance cholangiopancreatography) (55.9 %). Most prevalent morphologic findings included calcifications (35 %) and pseudocysts (27 %). Exocrine (38.8 %) and endocrine (35.2 %) pancreatic insufficiency had both a similar frequency. Treatments used were rather heterogeneous among sites, with enzyme replacement therapy (40.7 %) and insulin (30.9 %) being most commonly used. CONCLUSIONS: Pancreas units amass a significant number of both prevalent and incident CP cases. Patients seen in these units share a similar typology, and differences between units are greater regarding diagnostic and therapeutic strategies.

Early and/or immediately full caloric diet versus standard refeeding in mild acute pancreatitis: a randomized open-label trial.

UNLABELLED: Refeeding after acute pancreatitis (AP) is traditionally started in a successively increasing manner when abdominal pain is absent and pancreatic enzymes are decreasing. We aimed to evaluate length of hospital stay (LOHS) and refeeding tolerance for early refeeding and/or immediately full caloric intake in patients recovering from AP. METHODS: In this randomized, open-label trial, patients with AP were randomized into four different refeeding protocols. Group 1 and 2 received a stepwise increasing diet during three days while 3 and 4 received an immediately full caloric, low fat diet. Group 2 and 4 started refeeding early (once bowel sounds returned) and 1 and 3 started at standard time (bowel sounds present, no abdominal pain, no fever, leucocytes and pancreatic enzymes decreasing). Main outcomes measurements were LOHS and tolerance (ability to ingest >50% of meals without severe pain, nausea or AP relapse). RESULTS: Eighty patients were evaluated and 72 randomized (median age 60 years, range 24-85, 33 male). LOHS was significantly reduced after early refeeding (median 5 versus 7 days (p = 0.001)) but not in patients receiving immediately full caloric diet, compared to standard management (6 versus 6 days (p = 0.12)). There was no difference in refeeding tolerance comparing immediately full caloric diet versus stepwise increasing diet (31/35 (89%) versus 33/37 (89%) patients tolerating the treatment, p = 1.00) or early versus standard time for refeeding (33/37 (89%) versus 31/35 (89%), (p = 1.00)). CONCLUSIONS: Refeeding after AP when bowel sounds are present with immediately full caloric diet is safe and well tolerated. Early refeeding shortens LOHS.

The role of high fat diet in the development of complications of chronic pancreatitis.

BACKGROUND: Little is known about risk factors for complications in chronic pancreatitis (CP). High fat diet (HFD) has been demonstrated to aggravate pancreatic injury in animal models. The aim of this study was to investigate the role of HFD in age at diagnosis of CP and probability of CP related complications. METHODS: A cross-sectional case-case study was performed within a prospectively collected cohort of patients with CP. Diagnosis and morphological severity of CP was established by endoscopic ultrasound. Pancreatic exocrine insufficiency (PEI) was diagnosed by ¹³C mixed triglyceride breath test. Fat intake was assessed by a specific nutritional questionnaire. Odds ratios (OR) for CP related complications were estimated by multivariate logistic regression analysis. RESULTS: 168 patients were included (128 (76.2%) men, mean age 44 years (SD 13.5)). Etiology of CP was alcohol abuse in 89 patients (53.0%), other causes in 30 (17.9%) and idiopathic in the remaining 49 subjects (29.2%). 24 patients (14.3%) had a HFD. 68 patients (40.5%) had continuous abdominal pain, 39 (23.2%) PEI and 43 (25.7%) morphologically severe CP. HFD was associated with an increased probability for continuous abdominal pain (OR = 2.84 (95% CI, 1.06-7.61)), and a younger age at diagnosis (37.0 ± 13.9 versus 45.8 ± 13.0 years, p = 0.03) but not with CP related complications after adjusting for sex, years of follow-up, alcohol and tobacco consumption, etiology and body mass index. CONCLUSIONS: Compared with a normal fat diet, HFD is associated with a younger age at diagnosis of CP and continuous abdominal pain, but not with severity and complications of the disease.

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

The actual management of early pancreatic cancer.

Pancreatic cancer (PC) is a highly lethal disease. Early diagnosis remains the only possibility nowadays for an intention to cure the disease, since prognosis of PC is significantly better in patients diagnosed of small (<2 cm), well differentiated, stages I and II pancreatic tumors. However, the best approach would be to detect precursor lesions, like Intraductal papillary mucinous neoplasm (IPMN) or PanIN lesions. In this setting the best technique to diagnose either small PC and/or IPMN and PanIN lesions is clearly endoscopic ultrasound. However, detection of these lesions is very difficult, hampered by the absence of clinical manifestations of PC at these early stages. The implementation of screening programs, which - given the incidence of PC - is not cost effective for the general population, in high-risk individuals, may lead to increase the detection of PC an early stages as well as precursor lesion. When focusing on treatment, PC patients are best cared by multidisciplinary teams. For patients with resectable disease surgery remains the treatment of choice, followed by postoperative treatment. When precursor lesions are detected, mainly IPMN, treatment should be individualized, following latest international guidelines.

Early diagnosis of pancreatic cancer, time to screen high-risk individuals?

Pancreatic cancer (PC) is considered as one of the malignant tumors with poorest survival rate (less than 5% 5-year survival). Despite new developments in imaging techniques, surgery and oncologic treatments, survival rate remains unchanged. In order to improve the outcome of this disease, it would be of interest the development of a screening program trying to detect small asymptomatic tumors or precursor lesions at the time when the disease is still at a curable stage. Although screening in general population is not feasible nowadays, screening programs in high risk individuals may be of help in this setting. A specific population has been defined to be screened, those with a >10-fold increased risk for developing the disease (inherited PC syndromes due to inherited gene mutations and individuals with a strong family history of PC with at least 2 first-degree relatives affected, but without a known genetic defect). Regarding the methods for screening, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) appears to be the most accurate, mainly based in their ability to detect those small pancreatic tumors and precursor lesions (like IPMN and PanIN lesions). In these patients screening should start at the age of 45, or 15 years earlier than the earliest occurrence of PC in the family, whichever is the earlier age. Explorations should be schedule every 1 to 3 years, depending on initial findings.

Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that might characterize the differences of hardness and strain between diseased tissue and normal tissue. The aim of this study was to assess the efficiency of EUS elastography for the differentiation of focal masses in chronic pancreatitis and pancreatic cancer. PATIENTS AND METHODS: The study group comprised 258 patients with focal pancreatic masses included prospectively at 13 participating centers. Qualitative analysis of the diagnoses made by two expert doctors using all recorded video clips was performed in order to test the interobserver variability. A post-processing software analysis was used to examine the EUS elastography videos by calculating average-hue histograms of individual elastography images. The quantitative information was used to calculate intra-observer variability and the accuracy of the method. RESULTS: Qualitative analysis of the recorded videos revealed a kappa value of 0.72. Intra-observer variability analysis revealed that the single measure intraclass correlation ranged between 0.86 and 0.94. The average-hue histogram analysis of the data indicated a sensitivity of 93.4 %, a specificity of 66.0 %, a positive predictive value of 92.5 %, a negative predictive value of 68.9 %, and an overall accuracy of 85.4 %, based on a cut-off value of 175. Area under the receiver operating characteristic curve (AUROC) was 0.854 ( P < 0.0001) with a confidence interval of 0.804 - 0.894. CONCLUSION: The value of quantitative analysis of EUS elastography recordings was proven by good reproducibility of the videos, as well as good parameters of the AUROC analysis. (Clinical Trials.gov identifier: CT00909103).

Second-generation endoscopic ultrasound elastography in the differential diagnosis of solid pancreatic masses. Pancreatic cancer vs. inflammatory mass in chronic pancreatitis.

Endoscopic ultrasonography (EUS) is considered one of the most accurate methods for the diagnosis and staging of pancreatic tumors. EUS-guided fine-needle aspiration (FNA) allows to increase the diagnostic accuracy of EUS in this setting; however, it is technically demanding (a pathologist is also essential) and is furthermore associated with small, but not insignificant morbidity. EUS pancreatic elastography, by analyzing tissue stiffness, arises as a new and very useful tool for the differential diagnosis of solid pancreatic masses. Elastography provides specific patterns supporting the benign or malignant nature of the disease. However, there is a handicap related to the subjective interpretation of images. Second-generation elastography has been recently developed, and allows a quantitative analysis of tissue stiffness. It is based on the determination of a strain ratio (obtained after comparing the strain value of the mass to a strain value from a control area in the region under study). We present two cases reflecting the usefulness of second-generation elastography in the differential diagnosis between pancreatic adenocarcinoma and an inflammatory mass in the context of chronic pancreatitis. We found significant differences between both masses in the strain ratio values (25.46% in the pancreatic adenocarcinoma vs. 2.35% in the inflammatory mass). Second-generation elastography is a very useful tool for the differential diagnosis of solid pancreatic masses.

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer.

Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS) appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

Pancreatitis and systemic lupus erythematosus.

Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain. However, the rate of pancreatic diseases is much lower and does not reach 5% according to published series in Europe and the USA. This association between SLE and pancreatic disease is basically at the expense of episodes of acute pancreatitis. An association with chronic pancreatitis is much more uncommon, and only four articles have been published showing this relationship. Three cases of SLE-associated pancreatitis are described, and disease onset, etiological factors, and clinical progression are analyzed. A review of the literature and a brief discussion about pathophysiological mechanisms and the role of corticosteroids are also included.

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

Pancreatic cancer is the 5th leading cause of cancer-relateddeath in Western countries. The 5-year survival rate is approximately4%, without significant changes over the last 50 years.This poor survival rate and bad prognosis are associated with thediagnosis of advanced-stage disease, which precludes the only potentialcurative treatment – surgical resection. In this setting, themain objective in the management of pancreatic cancer is to performan early diagnosis and a correct staging of the disease. Endoscopicultrasonography (EUS) appears to be an essential toolfor the diagnosis and staging of pancreatic cancer. EUS diagnosticaccuracy for detecting pancreatic tumors ranges from 85 to100%, clearly superior to other imaging techniques. EUS accuracyfor the local staging of pancreatic cancer ranges from 70 to90%, superior or equivalent to other imaging modalities. EUSguidedfine-needle aspiration allows a cyto-histological diagnosisin nearly 90% of cases, with a very low complication rate. At present,the formal indications for EUS-guided fine-needle aspirationare the necessity of palliative treatment or whenever the possibilityof neoadjuvant treatment is present. It could be also indicated todifferentiate pancreatic adenocarcinoma from other pancreaticconditions, like lymphoma, metastasis, autoimmune pancreatitisor chronic pancreatitis. We can conclude that EUS is an essentialtool in the management of patients with pancreatic tumors(AU)

Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors.

In the presence of a pancreatic tumor, the main diagnostic problem is to determine the benign o malignant nature of the lesion, and then to evaluate its resectability. A preoperative biopsy was usually rejected based on the fact that negative results do not exclude malignancy, that such biopsy may hamper the possibility of curative surgery because of potential seeding along the biopsy s trajectory, that surgical morbidity and mortality are low, and also because of the high diagnostic sensitivity of the various imaging techniques. Biopsy for solid pancreatic tumors was limited to irresectable tumors, and isolated cases with suspicion of tuberculosis, lymphoma or neuroendocrine tumors. Nowadays the performance of a pancreatic biopsy is becoming essential for the correct management of solid lesions, and is useful not only to establish malignancy, but also for a better knowledge of all kind of pathologies and, thus, for better therapeutic management. In this context, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven a safe technique with a low rate of complications and a diagnostic accuracy superior to other procedures, this being considered the method of choice for the study of solid pancreatic lesions. An illustrative example is the case we report in this article -a patient diagnosed of a solid, locally advanced-stage pancreatic tumor with imaging techniques (abdominal ultrasounds and EUS) under EUS-guided FNA; the procedure could establish a final diagnosis of pancreatic fusocellular sarcoma.